tbuckley/cabot-search huggingface dataset:
Poly Ethylene Glycol (PEG)‐based Hydrogels for Drug Delivery in Cancer Therapy
Authors: Zihan Wang, Qinzhou Ye, Sheng Yu, Behnam Akhavan
Journal: Advanced Healthcare Materials (2023)

Hydrogel-based drug delivery systems (DDSs) can leverage therapeutically beneficial outcomes in cancer therapy. In this domain, polyethylene glycol (PEG) has become increasingly popular as a biomedical polymer and has found clinical use. Owing to their excellent biocompatibility, facile modifiability, and high drug encapsulation rate, PEG hydrogels have shown great promise as drug delivery platforms. Here, the progress in emerging novel designs of PEG-hydrogels as DDSs for anti-cancer therapy is reviewed and discussed, focusing on underpinning multiscale release mechanisms categorized under stimuli-responsive and non-responsive drug release. The responsive drug delivery approaches are discussed, and the underpinning release mechanisms are elucidated, covering the systems functioning based on either exogenous stimuli-response, such as photo- and magnetic-sensitive PEG hydrogels, or endogenous stimuli-response, such as enzyme-, pH-, reduction-, and temperature-sensitive PEG hydrogels. Special attention is paid to the commercial potential of PEG-based hydrogels in cancer therapy, highlighting the limitations that need to be addressed in future research for their clinical translation.
Clinical Importance of the lncRNA <i>NEAT1</i> in Cancer Patients Treated with Immune Checkpoint Inhibitors
Authors: Joseph Toker, J. Bryan Iorgulescu, Alexander L. Ling, Genaro R. Villa, Josephina A.M.A. Gadet, Laxmi Parida, Gad Getz, Catherine J. Wu, David A. Reardon, E. Antonio Chiocca, Marco Mineo
Journal: Clinical Cancer Research (2023)

mAbs targeting the PD-1/PD-L1 immune checkpoint are powerful tools to improve the survival of patients with cancer. Understanding the molecular basis of clinical response to these treatments is critical to identify patients who can benefit from this immunotherapy. In this study, we investigated long noncoding RNA (lncRNA) expression in patients with cancer treated with anti-PD-1/PD-L1 immunotherapy.lncRNA expression profile was analyzed in one cohort of patients with melanoma and two independent cohorts of patients with glioblastoma (GBM) undergoing anti-PD-1/PD-L1 immunotherapy. Single-cell RNA-sequencing analyses were performed to evaluate lncRNA expression in tumor cells and tumor-infiltrating immune cells.We identified the lncRNA NEAT1 as commonly upregulated between patients with melanoma with complete therapeutic response and patients with GBM with longer survival following anti-PD-1/PD-L1 treatment. Gene set enrichment analyses revealed that NEAT1 expression was strongly associated with the IFNγ pathways, along with downregulation of cell-cycle-related genes. Single-cell RNA-sequencing analyses revealed NEAT1 expression across multiple cell types within the GBM microenvironment, including tumor cells, macrophages, and T cells. High NEAT1 expression levels in tumor cells correlated with increased infiltrating macrophages and microglia. In these tumor-infiltrating myeloid cells, we found that NEAT1 expression was linked to enrichment in TNFα/NFκB signaling pathway genes. Silencing NEAT1 suppressed M1 macrophage polarization and reduced the expression of TNFα and other inflammatory cytokines.These findings suggest an association between NEAT1 expression and patient response to anti-PD-1/PD-L1 therapy in melanoma and GBM and have important implications for the role of lncRNAs in the tumor microenvironment.
Racial and Ethnic Disparities in Mpox Cases and Vaccination Among Adult Males — United States, May–December 2022
Authors: Krishna Kiran Kota, Jaeyoung Hong, Carla Zelaya, Aspen P. Riser, Alexia Rodriguez, Daniel L. Weller, Ian H. Spicknall, Jennifer L. Kriss, Florence Lee, Peter Boersma, Elizabeth Hurley, Peter Hicks, Craig Wilkins, Harrell Chesson, Jeniffer Concepción-Acevedo, Sascha Ellington, Ermias Belay, Jonathan Mermin
Journal: MMWR Morbidity and Mortality Weekly Report (2023)

As of December 31, 2022, a total of 29,939 monkeypox (mpox) cases* had been reported in the United States, 93.3% of which occurred in adult males. During May 10-December 31, 2022, 723,112 persons in the United States received the first dose in a 2-dose mpox (JYNNEOS)† vaccination series; 89.7% of these doses were administered to males (1). The current mpox outbreak has disproportionately affected gay, bisexual, and other men who have sex with men (MSM) and racial and ethnic minority groups (1,2). To examine racial and ethnic disparities in mpox incidence and vaccination rates, rate ratios (RRs) for incidence and vaccination rates and vaccination-to-case ratios were calculated, and trends in these measures were assessed among males aged ≥18 years (males) (3). Incidence in males in all racial and ethnic minority groups except non-Hispanic Asian (Asian) males was higher than that among non-Hispanic White (White) males. At the peak of the outbreak in August 2022, incidences among non-Hispanic Black or African American (Black) and Hispanic or Latino (Hispanic) males were higher than incidence among White males (RR = 6.9 and 4.1, respectively). Overall, vaccination rates were higher among males in racial and ethnic minority groups than among White males. However, the vaccination-to-case ratio was lower among Black (8.8) and Hispanic (16.2) males than among White males (42.5) during the full analytic period, indicating that vaccination rates among Black and Hispanic males were not proportionate to the elevated incidence rates (i.e., these groups had a higher unmet vaccination need). Efforts to increase vaccination among Black and Hispanic males might have resulted in the observed relative increased rates of vaccination; however, these increases were only partially successful in reducing overall incidence disparities. Continued implementation of equity-based vaccination strategies is needed to further increase vaccination rates and reduce the incidence of mpox among all racial and ethnic groups. Recent modeling data (4) showing that, based on current vaccination coverage levels, many U.S. jurisdictions are vulnerable to resurgent mpox outbreaks, underscore the need for continued vaccination efforts, particularly among racial and ethnic minority groups.
Assessment of Psilocybin Therapy for Patients With Cancer and Major Depression Disorder
Authors: Manish Agrawal, Ezekiel Emanuel, Brian Richards, William Richards, Kim Roddy, Paul Thambi
Journal: JAMA Oncology (2023)

This nonrandomized controlled trial used a 1-to-1 therapist-to-patient ratio to administer psilocybin to groups of patients with cancer who were diagnosed with major depression disorder to create a scalable, rapidly effective depression treatment.
mTORC2, a Novel “Twist” on the Epithelial Sodium Channel (ENaC)
Authors: David H. Ellison, James A. McCormick
Journal: Journal of the American Society of Nephrology (2023)

1Division of Nephrology and Hypertension, Department of Medicine, Oregon Health and Science University, Portland, Oregon 2Oregon Clinical and Translational Research Institute, Oregon Health and Science University, Portland, Oregon 3VA Portland Health Care System, Portland, Oregon Correspondence: Dr. David H. Ellison, Oregon Clinical and Translational Research Institute, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239. Email: [email protected] See related article, "Potassium Activates mTORC2-dependent SGK1 Phosphorylation to Stimulate Epithelial Sodium Channel: Role in Rapid Renal Responses to Dietary Potassium," on pages 1019–1038. Published online ahead of print. Publication date available at www.jasn.org.
The Role of Inflammation in the Initiation and Progression of Myeloid Neoplasms
Authors: Juan Carlos Balandrán, Audrey Lasry, Iannis Aifantis
Journal: Blood Cancer Discovery (2023)

Myeloid malignancies are devastating hematologic cancers with limited therapeutic options. Inflammation is emerging as a novel driver of myeloid malignancy, with important implications for tumor composition, immune response, therapeutic options, and patient survival. Here, we discuss the role of inflammation in normal and malignant hematopoiesis, from clonal hematopoiesis to full-blown myeloid leukemia. We discuss how inflammation shapes clonal output from hematopoietic stem cells, how inflammation alters the immune microenvironment in the bone marrow, and novel therapies aimed at targeting inflammation in myeloid disease.
The circadian protein BMAL1 supports endothelial cell cycle during angiogenesis
Authors: Matteo Astone, Roxana E Oberkersch, Giovanni Tosi, Alberto Biscontin, Massimo M Santoro
Journal: Cardiovascular Research (2023)

The circadian clock is an internal biological timer that co-ordinates physiology and gene expression with the 24-h solar day. Circadian clock perturbations have been associated to vascular dysfunctions in mammals, and a function of the circadian clock in angiogenesis has been suggested. However, the functional role of the circadian clock in endothelial cells (ECs) and in the regulation of angiogenesis is widely unexplored.Here, we used both in vivo and in vitro approaches to demonstrate that ECs possess an endogenous molecular clock and show robust circadian oscillations of core clock genes. By impairing the EC-specific function of the circadian clock transcriptional activator basic helix-loop-helix ARNT like 1 (BMAL1) in vivo, we detect angiogenesis defects in mouse neonatal vascular tissues, as well as in adult tumour angiogenic settings. We then investigate the function of circadian clock machinery in cultured EC and show evidence that BMAL and circadian locomotor output cycles protein kaput knock-down impair EC cell cycle progression. By using an RNA- and chromatin immunoprecipitation sequencing genome-wide approaches, we identified that BMAL1 binds the promoters of CCNA1 and CDK1 genes and controls their expression in ECs.Our findings show that EC display a robust circadian clock and that BMAL1 regulates EC physiology in both developmental and pathological contexts. Genetic alteration of BMAL1 can affect angiogenesis in vivo and in vitro settings.
Short-term topiramate treatment prevents radiation-induced cytotoxic edema in preclinical models of breast-cancer brain metastasis
Authors: Maria J Contreras-Zárate, Karen L F Alvarez-Eraso, Jenny A Jaramillo-Gómez, Zachary Littrell, Nikki Tsuji, D Ryan Ormond, Sana D Karam, Peter Kabos, Diana M Cittelly
Journal: Neuro-Oncology (2023)

Abstract Background Brain edema is a common complication of brain metastases (BM) and associated treatment. The extent to which cytotoxic edema, the first step in the sequence that leads to ionic edema, vasogenic edema, and brain swelling, contributes to radiation-induced brain edema during BM remains unknown. This study aimed to determine whether radiation-associated treatment of BM induces cytotoxic edema and the consequences of blocking the edema in preclinical models of breast-cancer brain metastases (BCBM). Methods Using in vitro and in vivo models, we measured astrocytic swelling, trans-electric resistance (TEER), and aquaporin 4 (AQP4) expression following radiation. Genetic and pharmacological inhibition of AQP4 in astrocytes and cancer cells was used to assess the role of AQP4 in astrocytic swelling and brain water intake. An anti-epileptic drug that blocks AQP4 function (topiramate) was used to prevent cytotoxic edema in models of BM. Results Radiation-induced astrocytic swelling and transient upregulation of AQP4 occurred within the first 24 hours following radiation. Topiramate decreased radiation-induced astrocytic swelling and loss of TEER in astrocytes in vitro, and acute short-term treatment (but not continuous administration), prevented radiation-induced increase in brain water content without pro-tumorigenic effects in multiple preclinical models of BCBM. AQP4 was expressed in clinical BM and breast-cancer cell lines, but AQP4 targeting had limited direct pro-tumorigenic or radioprotective effects in cancer cells that could impact its clinical translation. Conclusions Patients with BM could find additional benefits from acute and temporary preventive treatment of radiation-induced cytotoxic edema using anti-epileptic drugs able to block AQP4 function.
Prostate-Specific Antigen Screening Should Not Be Covered by Publicly Funded Health Insurance
Authors: Takeshi Takahashi
Journal: JAMA Oncology (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
The association between kidney function, cognitive function, and structural brain abnormalities in community-dwelling individuals aged 50+ is mediated by age and biomarkers of cardiovascular disease
Authors: Natalia Nowak, Celine De Looze, Aisling O’Halloran, Rose Anne Kenny, Donal J Sexton
Journal: Cardiovascular Research (2023)

Cognitive impairment has been associated with kidney function and chronic kidney disease. Whether this association is due to accelerated cardiovascular disease (CVD) or an independent specific kidney function effect related to toxins is unclear. We investigated the impact of an array of clinical factors, inflammatory biomarkers, and cardiovascular biomarkers on the association between kidney function, cognitive function, and structural brain abnormalities.We used data from the first and third waves of the TILDA Study, a population-representative prospective cohort of Irish adults aged 50 years and over, based on stratified random sampling (n = 3774). The MRI sub-study included participants who consented to MRI brain imaging in addition to the health assessment. Multivariable linear and mixed-effect longitudinal regression models were fitted separately for each kidney marker/estimated glomerular filtration rate (eGFR) equation after adjusting for baseline age and demographics, clinical vascular risk factors, and biomarkers. Unadjusted analyses showed an association between low eGFR, cognitive dysfunction, and cognitive decline (P < 0.001 for all kidney markers). Kidney function markers were also associated with white matter disease [OR = 3.32 (95% CI: 1.11, 9.98)], total grey matter volume (β = -0.17, 95% CI -0.27 to -0.07), and regional grey matter volumes within areas particularly susceptible to hypoxia (P < 0.001 for all). All the associations decreased after adjusting for age and were also diminished after adjusting for CVD biomarkers. Age and CVD-biomarker score were significant mediators of the adjusted associations between eGFR and cognitive status. These results remained consistent for cross-sectional and longitudinal outcomes and specific cognitive domains.Decreased kidney function was associated with cerebrovascular disease. The association appeared to be mediated predominantly by age and the combination of CVD markers [namely N-terminal pro-B-type natriuretic peptide (NT-proBNP) and Growth Differentiation Factor 15 (GDF15)], supporting the idea that shared biological pathways underline both diseases. Further mechanistic studies of the specific molecular mechanisms that lead to both kidney and cognitive decline are warranted.
<i>Notes From the Field:</i> Campylobacteriosis Outbreak Associated with Consumption of Raw Water — Montana, 2022
Authors: Rachel Hinnenkamp, Shawn Sorenson, Edward Evanson, Jonathan Yoder, Mia Mattioli
Journal: MMWR Morbidity and Mortality Weekly Report (2023)

Consumption of raw water (water that has not been disinfected or filtered) has become an emerging trend in the United States and could pose serious health consequences (1).Drinking water collected directly from outdoor freshwater sources such as lakes, rivers, and streams that has not been adequately treated (i.e., to remove pathogens) can cause disease and outbreaks (2).This report describes how a community in Western Montana responded to an outbreak of 19 cases of diarrheal illness associated with consuming untreated surface water.On May 9, 2022, Sanders County, Montana, reported to the state health department six active cases of Campylobacter infection in their community; this case count represented a substantial increase above the 5-year average of six reported cases annually during 2017-2021.All infected persons reported drinking water from watering point A, an outlet of surface water from a creek near Paradise, Montana (Figure ), before their onset of symptoms, which began on or after May 4.During the next 6 weeks, 13 additional cases of Campylobacter jejuni infection among persons exposed to the same water source were identified through laboratory testing (two by culture-independent confirmation and four by culture confirmation) or epidemiologic linkage (seven).One person was hospitalized, and no deaths were reported.On May 16, Sanders County Public Health environmental health staff members collected 23 liters of water from watering point A. The Montana Laboratory Services Bureau performed membrane filtration on 15 liters of the water sample, using four separate filters (0.45 μm [44 mm] pore size).The filters were then plated on media for Campylobacter culture and isolation following standard methods (3); investigators did not culture for or find any other pathogens.On May 24, the water sample was confirmed positive for Campylobacter by culture.On June 3, staff members performed whole genome sequencing on one Campylobacter isolate from the water sample and isolates from two human outbreak specimens; sequences were compared by both core genome multilocus sequence typing and whole genome multilocus sequence typing (4).Campylobacter isolates from the human specimens and water samples were highly genetically related (0-1 allele apart).Together, whole * https://www.cdc.gov/healthywater/drinking/travel/backcountry_water_treatment.html
Neuroprotective, neurogenic, and anticholinergic evidence of<i>Ganoderma lucidum</i>cognitive effects: Crucial knowledge is still lacking
Authors: Diandra A. Luz, Alana M. Pinheiro, Enéas A. Fontes‐Júnior, Cristiane S. F. Maia
Journal: Medicinal Research Reviews (2023)

Abstract Ganoderma lucidum is a mushroom that has been widely used for centuries in Asian countries for its antiaging properties. It is popularly known as “Ling Zhi,” “Reishi,” and “Youngzhi,” and because of its benefits, it is known as the “immortality mushroom.” Pharmacological assays have revealed that G. lucidum ameliorates cognitive impairments through inhibition of β‐amyloid and neurofibrillary tangle formation, antioxidant effect, reduction of inflammatory cytokine release and apoptosis, genic expression modulation, among other activities. Chemical investigations on G. lucidum have revealed the presence of metabolites such as triterpenes, which are the most explored in this field, as well as flavonoids, steroids, benzofurans, and alkaloids; in the literature, these have also been reported to have mnemonic activity. These properties of the mushroom make it a potential source of new drugs to prevent or reverse memory disorders, as actual medications are able to only alleviate some symptoms but are unable to stop the progress of cognitive impairments, with no impact on social, familiar, and personal relevance. In this review, we discuss the cognitive findings of G. lucidum reported in the literature, converging the proposed mechanisms through the several pathways that underlie memory and cognition processes. In addition, we highlight the gaps that deserve particular attention to support future studies.
Microbiota Influences on Hematopoiesis and Blood Cancers: New Horizons?
Authors: Jessica R. Galloway-Peña, Christian Jobin
Journal: Blood Cancer Discovery (2023)

Hematopoiesis governs the generation of immune cells through the differentiation of hematopoietic stem cells (HSC) into various progenitor cells, a process controlled by intrinsic and extrinsic factors. Among extrinsic factors influencing hematopoiesis is the microbiota, or the collection of microorganisms present in various body sites. The microbiota has a profound impact on host homeostasis by virtue of its ability to release various molecules and structural components, which promote normal organ function. In this review, we will discuss the role of microbiota in influencing hematopoiesis and how disrupting the microbiota/host network could lead to hematologic malignancies, as well as highlight important knowledge gaps to move this field of research forward.
Apoptosis: a<i>Janus bifrons</i>in T-cell immunotherapy
Authors: Yong Gu Lee, Nicholas Yang, Inkook Chun, Patrizia Porazzi, Alberto Carturan, Luca Paruzzo, Christopher Tor Sauter, Puneeth Guruprasad, Raymone Pajarillo, Marco Ruella
Journal: Journal for ImmunoTherapy of Cancer (2023)

Immunotherapy has revolutionized the treatment of cancer. In particular, immune checkpoint blockade, bispecific antibodies, and adoptive T-cell transfer have yielded unprecedented clinical results in hematological malignancies and solid cancers. While T cell-based immunotherapies have multiple mechanisms of action, their ultimate goal is achieving apoptosis of cancer cells. Unsurprisingly, apoptosis evasion is a key feature of cancer biology. Therefore, enhancing cancer cells’ sensitivity to apoptosis represents a key strategy to improve clinical outcomes in cancer immunotherapy. Indeed, cancer cells are characterized by several intrinsic mechanisms to resist apoptosis, in addition to features to promote apoptosis in T cells and evade therapy. However, apoptosis is double-faced: when it occurs in T cells, it represents a critical mechanism of failure for immunotherapies. This review will summarize the recent efforts to enhance T cell-based immunotherapies by increasing apoptosis susceptibility in cancer cells and discuss the role of apoptosis in modulating the survival of cytotoxic T lymphocytes in the tumor microenvironment and potential strategies to overcome this issue.
Age-dependent differences in efferocytosis determine the outcome of opsonophagocytic protection from invasive pathogens
Authors: Gavyn Chern Wei Bee, Kristen L. Lokken-Toyli, Stephen T. Yeung, Lucie Rodriguez, Tonia Zangari, Exene E. Anderson, Sourav Ghosh, Carla V. Rothlin, Petter Brodin, Kamal M. Khanna, Jeffrey N. Weiser
Journal: Immunity (2023)